Quinolones such as UHDBT (16) block mitochondrial electron transport in Saccaromyces cerevisiae and analog (17) was reported with potent in vitro MIC activity against C. albicans (3.2 ng/mL), C. tropicalis (0.8 ng/mL), C. kursi (0.4 iag/mL) and A. niger (6.3 ng/mL), while other analogs showed a marked decrease in potency (27). Reports of antifungal natural products include several diterpenes and withametelin from Datura metel (Solanaceae) leaves (28,29). Spiro pyrrolidines have been reported with antibacterial and antifungal activity (30). Finally, searching for new antifungal agents by the evaluation of known drugs not previously known for antifungal activity uncovered amiodarone (18), which is a known antiarrhythmic agent (31,32).
Genomics as a Tool in Discovery - Functional genomics by gene replacement and conditional expression (GRACE ) can identify essential gene products and can be used to identify antifungal compounds in a cell-based assay system (33,34). Moreover, proteomics and genomics offer emerging tools to assist in the rapid identification of essential fungal pathways and protein targets that can in turn be exploited by modern drug discovery programs (35,36).
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